Three-dimensional computer simulation of radiostereometric analysis (RSA) in distal radius fractures

Physical phantom models have conventionally been used to determine the accuracy and precision of radiostereometric analysis (RSA) in various orthopaedic applications. Using a phantom model of a fracture of the distal radius it has previously been shown that RSA is a highly accurate and precise method for measuring both translation and rotation in three-dimensions (3-D). The main shortcoming of a physical phantom model is its inability to mimic complex 3-D motion. The goal of this study was to create a realistic computer model for preoperative planning of RSA studies and to test the accuracy of RSA in measuring complex movements in fractures of the distal radius using this new model. The 3-D computer model was created from a set of tomographic scans. The simulation of the radiographic imaging was performed using ray-tracing software (POV-Ray). RSA measurements were performed according to standard protocol. Using a two-part fracture model (AO/ASIF type A2), it was found that for simple movements in one axis, translations in the range of 25microm-2mm could be measured with an accuracy of +/-2microm. Rotations ranging from 16 degrees to 2 degrees could be measured with an accuracy of +/-0.015 degrees . Using a three-part fracture model the corresponding values of accuracy were found to be +/-4microm and +/-0.031 degrees for translation and rotation, respectively. For complex 3-D motion in a three-part fracture model (AO/ASIF type C1) the accuracy was +/-6microm for translation and +/-0.120 degrees for rotation. The use of 3-D computer modelling can provide a method for preoperative planning of RSA studies in complex fractures of the distal radius and in other clinical situations in which the RSA method is applicable.     

Age related changes of soluble Fas, Fas ligand and Bcl-2 in autoimmune thyroid diseases

INTRODUCTION: Apoptosis plays a pivotal role in the regulation of immune mechanisms in the pathogenesis of autoimmune thyroid diseases (AITD). The prevalence of AITD increases with age. Purpose to compare soluble Fas, FasL and Bcl-2 in Graves disease (GD) and Hashimoto thyroiditis (HT) in relation to the age of the studied patients. MATERIAL AND METHODS: 3 groups of subjects: 1/25 patients with GD in euthyreosis on methimazol 2/27 patients with ChH in euthyreosis on levothyroxine. 3/12 healthy volunteers age and sex-matched to group 1-2. The serum levels of Fas, FasL and Bcl-2 were determined by the ELISA kit. RESULTS: We found positive correlations between sFas and age in GD patients (r = 0.35; p < 0.05). In GD patients we found a negative correlation between sFasL and age in all studied patients with AITD (r = -0.34; p < 0.01). We also found a negative correlation between sBcl-2 and age in HT patients (r = -0.42; p < 0.05). CONCLUSIONS: Fas/FasL and Bcl-2 signaling pathways seem to be age-related and may explain, at least in part, milder course of Graves disease in elderly patients and increased prevalence of Hashimoto disease in this group of subjects.     

A Hierarchical Regulatory Landscape during the Multiple Stages of EMT

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Anti-Inflammatory Activity of Choisya ternata Kunth Essential Oil,Ternanthranin, and Its Two Synthetic Analogs (Methyl and Propyl N-Methylanthranilates)

Choisya ternata Kunth (Rutaceae) is native to North America where it is popularly known as “Mexican orange”. In this study, the anti-inflammatory effects of the essential oil (EO) obtained from the leaves of C. ternata, one of its minor components (ternanthranin—ISOAN) and its two synthetic analogues (methyl and propyl N-methylanthranilate – MAN and PAN) were evaluated. Mice pretreated with the EO (EO) obtained from C. ternata leaves (3–100 mg/kg, p.o.), ISOAN, MAN or PAN (1–30 mg/kg, p.o.) and the reference drugs, morphine (1 mg/kg, p.o.) and acetylsalicylic acid (ASA, 100 mg/kg, p.o.), were evaluated in inflammation models such as formalin and subcutaneous air pouch models, with measurement of cell migration, exudate volume, protein extravasation, nitric oxide and pro-inflammatory cytokines. The EO from C. ternata significantly inhibited the time that the animals spent licking the formalin-injected paw in the second phase of the model at their higher doses (30 and 100 mg/kg, respectively). An inhibition of the inflammatory reaction induced after subcutaneous carrageenan injection into air pouch was also observed. In this model, the EO significantly reduced cell migration, exudate volume, protein extravased, and the increase in levels of inflammatory mediators (nitric oxide, TNF-α and IL-1β). ISOAN, MAN and PAN behaved in the same fashion at much smaller doses. Also, these molecules were able to show significant effects in the reduction of paw edema (at all tested doses) when the phlogistic agent was carrageenan, bradykinin, 5-HT, PGE2, C48/80 or 12-O-tetradecanoylphorbol-acetate (TPA). None of the tested doses had any effect in reducing histamine-induced edema. Our results indicate that the EO from C. ternata and anthranilate derivatives demonstrates an anti-inflammatory effect.     

Hotspots of Malaria Transmission in the Peruvian Amazon: Rapid Assessment through a Parasitological and Serological Survey

Background

With low and markedly seasonal malaria transmission, increasingly sensitive tools for better stratifying the risk of infection and targeting control interventions are needed. A cross-sectional survey to characterize the current malaria transmission patterns, identify hotspots, and detect recent changes using parasitological and serological measures was conducted in three sites of the Peruvian Amazon.

Material and Methods

After full census of the study population, 651 participants were interviewed, clinically examined and had a blood sample taken for the detection of malaria parasites (microscopy and PCR) and antibodies against P. vivax (PvMSP1₁₉, PvAMA1) and P. falciparum (PfGLURP, PfAMA1) antigens by ELISA. Risk factors for malaria infection (positive PCR) and malaria exposure (seropositivity) were assessed by multivariate survey logistic regression models. Age-specific seroprevalence was analyzed using a reversible catalytic conversion model based on maximum likelihood for generating seroconversion rates (SCR, λ). SaTScan was used to detect spatial clusters of serology-positive individuals within each site.

Results

The overall parasite prevalence by PCR was low, i.e. 3.9% for P. vivax and 6.7% for P. falciparum, while the seroprevalence was substantially higher, 33.6% for P. vivax and 22.0% for P. falciparum, with major differences between study sites. Age and location (site) were significantly associated with P. vivax exposure; while location, age and outdoor occupation were associated with P. falciparum exposure. P. falciparum seroprevalence curves showed a stable transmission throughout time, while for P. vivax transmission was better described by a model with two SCRs. The spatial analysis identified well-defined clusters of P. falciparum seropositive individuals in two sites, while it detected only a very small cluster of P. vivax exposure.

Conclusion

The use of a single parasitological and serological malaria survey has proven to be an efficient and accurate method to characterize the species specific heterogeneity in malaria transmission at micro-geographical level as well as to identify recent changes in transmission.     

Interfacial and lipid transfer properties of human phospholipid transfer protein: implications for the transfer mechanism of phospholipids

In circulation the phospholipid transfer protein (PLTP) facilitates the transfer of phospholipid-rich surface components from postlipolytic chylomicrons and very low density lipoproteins (VLDL) to HDL and thereby regulates plasma HDL levels. To study the molecular mechanisms involved in PLTP-mediated lipid transfer, we studied the interfacial properties of PLTP using Langmuir phospholipid monolayers and asymmetrical flow field-flow fractionation (AsFlFFF) to follow the transfer of 14C-labeled phospholipids and [35S]PLTP between lipid vesicles and HDL particles. The AsFlFFF method was also used to determine the sizes of spherical and discoidal HDL particles and small unilamellar lipid vesicles. In Langmuir monolayer studies high-activity (HA) and low-activity (LA) forms of PLTP associated with fluid phosphatidylcholine monolayers spread at the air/buffer interphase. Both forms also mediated desorption of [14C]dipalmitoylphosphatidylcholine (DPPC) from the phospholipid monolayer into the buffer phase, even when it contained no physiological acceptor such as HDL. After the addition of HDL3 to the buffer, HA-PLTP caused enhanced lipid transfer to them. The particle diameter of HA-PLTP was approximately 6 nm and that of HDL3 approximately 8 nm as determined by AsFlFFF analysis. Using this method, it could be demonstrated that in the presence of HA-PLTP, but not LA-PLTP, [14C]DPPC was transferred from small unilamellar vesicles (SUV) to acceptor HDL3 molecules. Concomitantly, [35S]-HA-PLTP was transferred from the donor to acceptor, and this transfer was not observed for its low-activity counterpart. These observations suggest that HA-PLTP is capable of transferring lipids by a shuttle mechanism and that formation of a ternary complex between PLTP, acceptor, and donor particles is not necessary for phospholipid transfer.     

Statistical tests for intra-tumour clonal co-occurrence and exclusivity

Tumour progression is an evolutionary process in which different clones evolve over time, leading to intra-tumour heterogeneity. Interactions between clones can affect tumour evolution and hence disease progression and treatment outcome. Intra-tumoural pairs of mutations that are overrepresented in a co-occurring or clonally exclusive fashion over a cohort of patient samples may be suggestive of a synergistic effect between the different clones carrying these mutations. We therefore developed a novel statistical testing framework, called GeneAccord, to identify such gene pairs that are altered in distinct subclones of the same tumour. We analysed our framework for calibration and power. By comparing its performance to baseline methods, we demonstrate that to control type I errors, it is essential to account for the evolutionary dependencies among clones. In applying GeneAccord to the single-cell sequencing of a cohort of 123 acute myeloid leukaemia patients, we find 1 clonally co-occurring and 8 clonally exclusive gene pairs. The clonally exclusive pairs mostly involve genes of the key signalling pathways.     

Three‐dimensional stratification pattern in an old‐growth lowland forest: How does height in canopy and season influence temperate bat activity?

The study of animal–habitat interactions is of primary importance for the formulation of conservation recommendations. Flying, gliding, and climbing animals have the ability to exploit their habitat in a three‐dimensional way, and the vertical canopy structure in forests plays an essential role for habitat suitability. Forest bats as flying mammals may seasonally shift their microhabitat use due to differing energy demands or changing prey availability, but the patterns are not well understood. We investigated three‐dimensional and seasonal habitat use by insectivorous bats in a temperate lowland old‐growth forest, the Belovezhskaya Pushcha in Belarus. We acoustically sampled broadleaved and mixed coniferous plots in the forest interior and in gaps in three heights during two reproductive periods (pregnancy/lactation vs. postlactation). In canopy gaps, vertical stratification in bat activity was less pronounced than in the forest interior. Vertical activity patterns differed among species. The upper canopy levels were important foraging habitats for the open‐space forager guild and for some edge‐space foragers like the Barbastelle bat Barbastella barbastellus and the soprano pipistrelle Pipistrellus pygmaeus. Myotis species had highest activity levels near the ground in forest gaps. Moreover, we found species‐dependent seasonal microhabitat shifts. Generally, all species and species groups considered except Myotis species showed higher activity levels during postlactation. Myotis species tended toward higher activity in the forest interior during postlactation. P. pygmaeus switched from high activity levels in the upper canopy during pregnancy and lactation to high activity levels near the ground during postlactation. We conclude that a full comprehension of forest bat habitat use is only possible when height in canopy and seasonal patterns are considered.